Every autumn nearly 6,000 students attend the iGEM – the International Genetically Engineered Machine competition – jamboree in Boston, Massachusetts. While most attendees are university students who have spent their summer preparing their projects, for the past five years Taipei American School (TAS) has entered a team. The remit is to tackle an everyday issue and come up with solution using molecular biology techniques.

The TAS team’s 2018 research topic caught our eye here at The News Lens. The team of senior high students aims to find a solution to the Asian Glow Syndrome. It is estimated that nearly 50 percent of the Taiwanese population has a deficiency of the gene ALDH2, which causes flushing after consuming alcohol.

While most people regard this as a purely cosmetic issue, and indeed one that people can overcome over time, the TAS team are keen to spread the word that the glow is a sign of a greatly increased risk of oral cancers – up to a 400 percent increase in some cases – and as such is an issue that deserves attention at a governmental level.


Credit: TAS

Participating in the Taiwan Alcohol Intolerance Education Society workshop with Justin W., Yvonne W., Charlotte C., Longan S. and Emily T.

The News Lens spoke to team member Emily T., who is in charge of public outreach for the team, about their efforts in in researching the issue and reaching out to various agencies to encourage better public education on the issue, and of course about the solution that they will present at this year’s jamboree from Oct. 18-24. Could this be a medical breakthrough by TAS that will help millions of Asians around the world?

The News Lens: You’ve chosen an interesting research topic for this year’s entry into the competition. How did you come up with this idea?

TAS iGEM Team: We were first introduced to ALDH2 deficiency when a guest speaker, Dr. Che-Hong Chen, was invited to speak at our school’s research speaker series. Dr. Chen is currently researching ALDH2 deficiency at Stanford University. We were not aware that such a high percentage, nearly 50 percent, of the Taiwanese population were at a higher risk of head, neck and throat cancer due to the inability to break down alcohol properly in the body. After understanding the severity of this in our home country, we felt compelled to tackle the issue.

TNL: This choice of topic might strike some people as an odd choice for high school students. Did you encounter any resistance to the choice?

TAST: When we proposed the topic to our teachers and school administration, we were met with support and enthusiasm rather than resistance. Throughout the year we had a variety of chances to spread awareness about our project at our school’s spring fair, class meetings and a bioethics discussion. We were even allowed to incorporate a discussion about the health implications of ALDH2 deficiency into the school’s health and physical education curriculum. Education and outreach is important at all ages, and we are happy to have the support of our community on this project.


Credit: TAS

The iGEM team, featuring: Tim H, Catherine C., Leona T., Iris H., Emily T., Caroline C., Charlotte C., Longan S., Ben W., Chloe W., Justin W. and Justin L.

TNL: As part of your research you spent some time contacting hospitals in Taiwan to find out if they offered testing for ALDH2 deficiency. What did you find out?

TAST: To find out what is currently being done about ALDH2 deficiency by our healthcare systems, we talked to a medical doctor, Dr. Stephanie Hsieh, and called multiple hospitals in Taiwan. We were surprised to find that the vast majority of hospitals in Taiwan do not have any form of testing for ALDH2 deficiency, and the few that did required extensive blood tests and were expensive (approximately US$70). This helped reaffirm the need to both raise awareness of and actually develop a treatment for the adverse health effects of ALDH2 deficiency.

TNL: You ran a survey around Taipei about the perceptions of the public regarding this issue. What did you discover?

TAST: We created a survey covering a broad spectrum of questions and received close to 700 (n=697) responses. Our survey was written and presented in both English and Mandarin to ensure that everyone could understand the questions. People of all ages were surveyed for the most diverse and unbiased results.

Our data shows clear signs of misconception and misunderstandings about the causes and resulting health risks of ALDH2 deficiency. For example, many people thought that turning red is the result of low alcohol tolerance, healthy liver functions, and fast metabolism — this is the opposite of the truth! These findings suggest a need for more public awareness about the health implications of ALDH2 deficiency.


Credit: TAS

The survey sourced responses from a broad sample of ages.

The results of our survey also helped us shape our final product design. Since we want to combat acetaldehyde buildup in the mouth, head, and neck regions (where the increased cancer risks are highest), we considered treatment options targeting these areas, such as oral medication, probiotics, or nasal sprays.

When asked the preferred method of treatment, we found that 53.4 percent of the people preferred using probiotics as the method of delivery. Since probiotics are commonly used, beneficial, and most importantly, safe to consume, it is no surprise that this is preferred method of treatment. In addition, most people preferred treatment only when they drink (as opposed to taking a product daily, weekly, etc.). We used all of this information to design our final ALDH2 delivery product, a probiotic throat lozenge that remains in the mouth, which can be consumed before or during drinking.

TNL: You have incorporated interviews and site visits with alcohol manufacturers into your background research. How did they respond to your project? Were they already aware of the high prevalence and health risks of ALDH2 deficiency in Taiwan?

TAST: When we spoke to alcohol manufacturers, we mainly wanted to learn more about their current policies on alcohol warning labels. In our research, we found that alcohol manufacturers can choose between five different labels to put on their products. To learn which ones are used and why, we asked alcohol manufacturers in Taiwan the following questions:

1. Which required warning statement (listed below) do you use? Why was it chosen?

a) Excessive consumption of alcohol is harmful to health 飲酒過量, 有害健康

b) To be safe, don't drink and drive.酒後不開車, 安全有保障。

c) Excessive drinking is harmful to you and others 飲酒過量, 害人害己。

d) Drinking is prohibited if under 18 years old 未滿十八歲者, 禁止飲酒。

e) Large quantity intake of alcohol product in a short period of time is lethal 短時間內大量灌酒會使人立即喪命。

2. Do you believe warning labels affect alcohol sales?

3. Would you be willing to exclusively use the health risk warning label (“Excessive consumption of alcohol is harmful to health”) in the future? Why or why not?

About half of the manufacturers responded. The most commonly used label was d) Drinking is prohibited if under 18 years old (未滿十八歲者, 禁止飲酒). When asked if they would place warning labels for health risks (“Excessive consumption of alcohol is harmful to health”), they mostly responded that they would comply if the government requested. They also believe that warning labels do not affect alcohol sales.


Credit: TAS

Simple bandage tests for ALDH2 deficiency in school with Emily T. and Catherine C.

TNL: You have contacted the Ministry of Finance and the Ministry of Health about improving the level of education and warning labels on products surrounding this issue. How did you feel about their response?

TAST: We were excited to receive responses from both ministries. We were also happy to hear that they will keep our suggestions in mind when developing new regulations. In the future, we hope that we can continue to work with both ministries to take more concrete action in strengthening alcohol warning label regulations. Ideally, we would like to see alcohol warning labels match the strict regulations already in place for tobacco products.

TNL: Can you briefly outline the scope of your research so far? Are you close to finding a workable treatment that might help those that suffer from the condition?

TAST: So far, we have successfully synthesized DNA of both the normal and the mutant ALDH2 genes, and tested the functions of the resulting enzymes. The normal ALDH2 enzymes that we made is about 3.5 times more efficient than the mutant ALDH2 at breaking down acetaldehyde, the toxic byproduct of alcohol metabolism. We also engineered a safe and commonly used probiotic strain, Escherichia coli Nissle 1917, to produce the normal ALDH2 enzyme, and tested its function under realistic conditions (in artificial saliva at body temperature).

We are now putting the ALDH2 probiotic into a candy (like a throat lozenge) to make sure ALDH2 is delivered into and remains in the mouth to lower the increased cancer risks that mainly occur in the oral, head and neck regions. We are also using mathematical modeling to determine how much probiotics should be used in the candy, and the amount of the acetaldehyde that will be metabolized as a result.


Credit: TAS

Experimental work in the lab with Catherine C.

TNL: Your research seems focused on finding an orally administered solution to the gene deficiency? Why is this?

TAST: Though we know alcohol is mainly metabolized in one’s liver, the deficiency is not directly correlated to liver cancer; instead, the deficiency is mainly linked to increased cancer risks in the upper digestive tract (esophageal cancer, head and neck cancer). Knowing this, we wanted to create a treatment that would stay in one’s mouth.

We were also interested in learning about the preferred delivery method for consumers, so we included a question in our survey: “Assuming we are able to engineer a solution to this deficiency, what would be your preferred method of application?” Of the options (oral medication, nasal spray, probiotics, none, or other), 30 percent of those surveyed voted for oral medication and 53 percent voted for probiotic treatment. Hence, we combined the two and decided to create a probiotic oral treatment!

TNL: If you are successful in developing a product that can be brought to market, it seems it might be very popular – particularly in countries where a high percentage of the population is affected, such as Taiwan, Japan, and South Korea. Have you thought about applying for a patent?

TAST: We have definitely thought about commercializing our product and have already drafted a business plan to guide us through the process. We reached out to Dr. Vera Wu, former Global Asset Lead at Pfizer, to learn more about drug development and marketing. Dr. Wu walked us through the three stages of drug development: discovery & research, development, and manufacturing. Mrs. Michelle Bruce, our business and marketing teacher, then guided us through the final process of developing a marketing plan for our potential product. In our marketing plan, we formulated a description for our envisioned product, conducted a market analysis, and examined the regulations required for our product to be approved for sale.


Credit: TAS

Interviewing Dr. Wu for the marketing plan with Nicole C., Austin H., Emily T. (left to right).

For further information on the competition, including academic papers on ALDH2 deficiency and instructions for self-testing for the deficiency (other than drinking a can of beer), please visit here.

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Editor: David Green (@DavidPeterGreen)

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